The present invention relates generally to chemical instrumentation and, more particularly, to centrifuges. A major objective of the present invention is to provide an improved centrifuge with tilt (i.e., rotation relative to gravitational or centrifugal force) control relative to the centrifugal force generated by the centrifuge.
The standard of living in modern societies has been greatly enhanced by advances in chemical, biological, and medical sciences. These fields all involve the separation of samples into constituent components that may then be processed to aid in their identification and/or quantification. The centrifuge is an important instance of instrumentation used to separate s ample components .
In addition, as described below, centrifuges that can control the tilt of a sample container relative to the centrifugal force can be used for pouring, mixing, filtering, and facilitating chemical reactions. Furthermore, tilting can be used to control liquid movement among multiple processing chambers of a sample container so that a series of processes can be implemented without manual intervention. Thus, a centrifuge with tilt control can automate sample processing conventionally performed manually by chemists.
A simple centrifuge has a centrifuge rotor that is spun, e.g., by a motor. Typically, a liquid-sample container spins with the rotor. The spinning sample components are subjected to a centrifugal force (F=mxcfx892r) proportional to their mass, their distance from the centrifuge spin axis, and the square of the spin rate. The effect of the centrifugal force is much like the effect of gravity-liquid components are separated according to their relative densities. However, unlike gravity, the centrifugal force is readily controlled, e.g., by controlling the spin rate. Thus, a centrifuge can generate centrifugal forces orders of magnitude greater than gravity at the earth""s surface. Generally, the xe2x80x9csupergravityxe2x80x9d conditions of a centrifuge are much more effective than gravity in separating sample components.
As suggested above, the supergravity conditions offered by centrifuges have uses other than component separation. Often the quantities of a sample available for analysis or processing are quite small. In the context of small sample volumes and the corresponding small capacities of the carrying the samples, surface tension limits liquid movement. The surface tension can make it difficult to flow a liquid from point to point as required for a series of processing steps or to mix a liquid as may be required to promote a reaction. The following three references disclose various approaches to tilting a sample container on a centrifuge relative to the centrifugal force. In each case, the tilting is used to control the movement of sample from chamber to chamber in a multi-chamber sample container to facilitate a series of reactions.
U.S. Pat. No. 5,089,417 to Wogoman discloses a centrifuge in which a holder for a sample container snaps from a first tilt orientation to a second tilt orientation when the centrifuge exceeds a predetermined rotation rate. Similarly, the first tilt orientation is resumed when the centrifuge spin rate falls below the threshold rate. Thus by increasing and decreasing the centrifuge spin rate, sample movement between reaction chambers of the sample container can be controlled. However, this approach provides little flexibility in selecting the centrifuge spin rate or tilt angles relative to the centrifugal force. It would be preferable to control the centrifuge rotation and the tilt actions independently.
Independent control of centrifuge spin rate and tilt action is disclosed in U.S. Pat. No. 4,814,282 to Holen et al. Similar to Wogomon, tilt of a sample container is used to transfer liquid from one chamber to another under the influence of centrifugal force. A tilt drive assembly, including motor and drive chain, is attached to the centrifuge rotor so that it rotates therewith. Power is delivered to the tilt-drive motor via slip rings, which tend to wear out as they are not generally designed to operate at centrifuge speeds. In this approach, any sensors used to track tilt would also rotate at high speeds, further complicating operation. In addition, centrifuge forces are applied to the tilt motor and drive train. For example, a 1-pound motor must withstand 1000-pound forces in a readily achievable 1000 G supergravity field. Thus, there are a number of robustness issues that can only be addressed with additional complexity and expense. U.S. Pat. No. 4,776,832 to Martin et al. avoids the need for physical connections to drive a tilt rotor by using inductive motors. The inductive motors include induction rotors that are physically coupled to holders, e.g., for reaction cells, and stationary stators, which are located beneath the centrifuge rotor (wheel). The stators induce eddy currents in the induction rotors, causing them to rotate. No physical connection is required between the stators and the induction rotors, eliminating the need to deliver power through slip rings. On the other hand, the non-physical coupling of drive and induction rotor does not ensure precise and flexible control of sample-container orientation relative to the supergravity field.
Related U.S. patent application Ser. No. 09/514,975, which is incorporated by reference herein in its entirety, teaches that agitating a sample container under centrifuge-induced supergravity conditions can overcome surface-tension to achieve rapid and thorough mixing. Such mixing can be invaluable in promoting many types of reactions, e.g., array hybridization.
Unfortunately, none of the three patents previously mentioned disclose centrifuges well adapted for this purpose. Wogomon lacks independent control over centrifuge spin rates and tilt angles. Holen does not provide sufficiently robust and precise control over tilt angle in view of the high speeds the tilt motor and any associated sensors must spin at. Martin lacks prescise control over tilt angle in view of the lack of a mechanical connnection between the tilt stators and the tilt rotors. What is needed is an economical and robust centrifuge that provides for independent and precise control of the tilt angle of a sample container relative to a spinning centrifuge rotor.
The present invention provides a coaxial-drive centrifuge with tilt control for manipulating liquid samples under supergravity conditions. The coaxial-drive arrangement allows a purely mechanical coupling between a stationary tilt motor to a tilt rotor that rotates relative to a rotating centrifuge rotor. The coaxial drive elements can be aligned with the axis of rotation for the centrifuge rotor. Appropriate gearing between the coaxial tilt-drive element, e.g., a shaft, and the tilt rotor allows the tilt axis to be displaced from the centrifuge axis. A sample container can be attached to the tilt rotor so that the angle of the container relative to the centrifugal force can be controlled to promote mixing or movement of the liquid contents of the container.
The invention provides for precise motion control. The centrifuge and tilt motors can be servo controlled. (Alternatively, high-speed stepper motors can be used.) The tilt motor is preferably phase-locked to the centrifuge motor. The desired positive and negative tilts relative to the centrifugal force can be added to the centrifuge servo angle to provide appropriate differential-drive commands to the tilt motor.
In a preferred realization of the invention, the tilt axis is parallel to and displaced from the centrifuge axis. Alternatively, the invention provides for any orientation of the tilt axis relative to the centrifuge axis, although, for most applications, the tilt axis is more parallel to the centrifuge axis than orthogonal to it.
In the case of parallel axes and a planar sample container, the plane of the container can be orthogonal to the tilt axis or generally orthogonal to the centrifugal force. The later orientation works best for agitating a sample by tilting back and forth so as to promote mixing. The former orientation works best for controlling the flow of a sample through a maze of chambers in the sample container. While sample motion control is provided in the prior art, the present invention allows much greater flexibility in the design of the maze since tilt angle is precisely controllable. In either case, the desired motion is achieved using a simple and robust mechanical linkage for both centrifuge and agitation motions. These and other features and advantages of the invention are apparent from the description below with reference to the following drawings.